Relmacabtagene Autoleucel Combined With Sintilimab for Relapsed/Refractory B-cell Lymphoma

Official title

A Single-arm, Phase II Clinical Study of Relmacabtagene Autoleucel Combined With Sintilimab for Relapsed/Refractory B-cell Lymphoma.

Overview

This is a prospective, single-arm, multicenter, phase II clinical trial to evaluate the efficacy and safety of Relmacabtagene Autoleucel in combination with the Sintilimab regimen for the treatment of relapsed/refractory B-cell lymphoma

Detailed description

Relmacabtagene Autoleucel treatment: Patients will receive intravenous fludarabine (25 mg/m²/day for 3 days) and cyclophosphamide (250 mg/m²/day for 3 days) for lymphodepletion, with adjustments based on hematologic and renal function.Relmacabtagene Autoleucel will be reinfused 2 to 7 days after lymphodepletion.

Sintilimab treatment: Patients will receive intravenous Sintilimab (200 mg every 3 weeks) starting on Day 28 after reinfusion, continuing until disease progression or intolerable toxicity, with a maximum duration of 1 year.

Primary endpoint: The complete response rate (CRR) at 3 months.

Interventions

• Drug Autoleucel (Relmacabtagene Autoleucel)
  Relmacabtagene Autoleucel will be reinfused 2 to 7 days after lymphodepletion (fludarabine + cyclophosphamide).
• Drug Sintilimab (PD-1 inhibitor)
  Patients will receive intravenous Sintilimab (200 mg every 3 weeks) starting on Day 28 after reinfusion, continuing until disease progression or intolerable toxicity, with a maximum duration of 1 year.

Primary outcome measures

• The complete response rate (CRR) at 3 months [Time frame: Up to 3 months after Relmacabtagene Autoleucel infusion]

Secondary outcome measures (5)

• Disease-free survival (DFS) [Time frame: From the date of the first complete response to the date of the first documented progression or death from any cause, whichever came first,assessed up to 24 months]
• Progression-free survival (PFS) [Time frame: From the date of enrollment until the date of the first documented progression or death from any cause,whichever came first,assessed up to 24 months]
• Overall survival (OS) [Time frame: From the date of enrollment until the date of death from any cause, assessed up to 24 months]
• Number of participants with adverse events (AE) and severe adverse events (SAE) as assessed by CTCAE v5.0 [Time frame: Through study completion, an average of 2 years]
• Objective Response Rate [Time frame: Up to 1 year after Relmacabtagene Autoleucel infusion]

Eligibility criteria

Inclusion criteria

• The patient must be aware of and voluntarily sign the informed consent form (ICF).
• Aged between 18 and 70 years, both male and female.
• Pathologically diagnosed with DLBCL, FL, or MCL, with histological confirmation of CD19 positivity (immunohistochemistry or flow cytometry, with flow cytometry used for re-evaluation if immunohistochemistry is CD19-negative).
• The patient must be willing to receive regorafenib and sintilimab treatment and be deemed suitable for this treatment by the investigator.
• Relapsed/refractory DLBCL, FL, or MCL.
• At least one measurable or evaluable lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
• Expected survival of ≥3 months.
• Adequate function of the heart, lungs, liver, kidneys, and other organs.

Exclusion criteria

• History of another malignancy that has not been in complete remission for at least 2 years, except for: non-melanoma skin cancer, completely resected stage I tumors with low recurrence potential, treated localized prostate cancer, biopsy-confirmed cervical carcinoma in situ, or squamous intraepithelial lesions detected by Pap smear and so on.
• Active Hepatitis B: a) Positive for Hepatitis B surface antigen (HBsAg) and/or Hepatitis B core antibody (HBcAb) , with HBV-DNA below the lower limit of the reference value can be included.
• Hepatitis C, HIV, or syphilis infection.
• Uncontrolled systemic fungal, bacterial, viral, or other infections.
• Acute or chronic graft-versus-host disease (GVHD).
• Known hypersensitivity or allergy to any study drug or excipient.
• Clinically significant central nervous system (CNS) disease or symptoms, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychiatric illness.
• Pregnant or breastfeeding women, and women of childbearing age who do not wish to use contraception.
• Mentally ill individuals or those unable to provide informed consent.
• The investigator deems the patient unsuitable for the study due to medical, psychological, familial, social, or geographical reasons or an inability to comply with the study protocol.
• Previous CAR-T cell therapy or other gene-modified T-cell treatments.
• Previous CD19-targeted therapy.
• Previous allogeneic hematopoietic stem cell transplantation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 3 centers

• Sun Yat-sen Universitiy Cancer Center — Guangzhou
• Fifth Affiliated Hospital of Guangzhou Medical University — Guangzhou
• Guangzhou overseas Chinese hospital — Guangzhou

Identifiers

NCT: NCT07077512 · B2025-263-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗